Girdle dystrophy 1A

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Classification according to ICD-10
G71.0 Muscular dystrophy
- pelvic or shoulder girdle shape
ICD-10 online (WHO version 2019)

The limb-1A (LGMD1A) is a very rare disease from the group of limb-girdle muscular dystrophy . The LGMD1A is caused by mutations in MYOT gene (human chromosome 5, 5q31.2) gives and autosomal - dominant inherited. MYOT codes for the protein myotilin , which can be found mainly in striated muscles ( skeletal and heart muscles ). An important function is the connection of actin filaments (so-called "cross-linking") in the area of ​​the Z-disk of muscle cells . In addition, myotilin plays a role in the formation of myofibrils ( myofibrillinogenesis ). So far there are only a few case reports. Four mutations in the MYOT gene are known which lead to the LGMD1A phenotype. Three of the four mutations have been described in members of two North American families with German and Argentine ancestors and one Turkish family. Another mutation has been detected in a single Japanese.

Clinically, the disease is characterized by initially proximal muscle weakness, which usually manifests itself in the third decade of life. The distal muscles are also affected as the disease progresses . In addition to muscle weakness, speech disorders ( dysarthria ) with nasal pronunciation, narrow Achilles tendons and a creatine kinase that is up to 15 times higher are typical. Weakened muscle reflexes have also been described.

In addition to girdle dystrophy, myotilin gene mutations have also been found in other diseases. These lead to a disease from the group of myofibrillary myopathies , myofibrillary myopathy 3 (MFM3). This is characterized by a later manifestation of the disease and by muscle parts that are primarily affected distally. LGMD1A and MFM3 are also known as myotilinopathies because of their common cause, namely mutations in the MYOT gene . Cases have also been described in which the two phenotypes overlap.

literature

  • D. Selcen, AG Engel: Myofibrillar myopathies. In: Robert Griggs: Muscular Dystrophies. (= Handbook of Clinical Neurology. Volume 101). 3. Edition. Elsevier, 2011, ISBN 978-0-08-045031-5 , p. 149.

Web links

Individual evidence

  1. ↑ Myotilin.  In: Online Mendelian Inheritance in Man . (English)
  2. ↑ UniProt Q9UBF9
  3. ↑ MA Hauser, SK Horrigan u. a .: Myotilin is mutated in limb girdle muscular dystrophy 1A. In: Human molecular genetics . Volume 9, Number 14, September 2000, pp. 2141-2147, ISSN  0964-6906 . PMID 10958653 .
  4. ^ MA Hauser, CB Conde u. a .: Myotilin Mutation found in second pedigree with LGMD1A. In: American Journal of Human Genetics . Volume 71, Number 6, December 2002, pp. 1428-1432, ISSN  0002-9297 . doi: 10.1086 / 344532 . PMID 12428213 . PMC 378586 (free full text).
  5. ↑ P. Reilich, S. Krause u. a .: A novel mutation in the myotilin gene (MYOT) causes a severe form of limb girdle muscular dystrophy 1A (LGMD1A). In: Journal of neurology. Volume 258, Number 8, August 2011, pp. 1437-1444, ISSN  0340-5354 . doi: 10.1007 / s00415-011-5953-9 . PMID 21336781 .
  6. ^ E. Pegoraro, EP Hoffman: Limb-Girdle Muscular Dystrophy Overview. GeneReviews [Internet]. University of Washington, Seattle, June 8, 2000, [updated August 30, 2012]. PMID 20301582 .
  7. ↑ D. Selcen, AG Engel: Mutations in myotilin cause myofibrillar myopathy. In: Neurology. Volume 62, Number 8, April 2004, pp. 1363-1371, ISSN  1526-632X . PMID 15111675 .
  8. ^ Myofibrillary Myopathy 3.  In: Online Mendelian Inheritance in Man . (English)
  9. ↑ M. Olivé, LG Goldfarb a. a . : Myotilinopathy: refining the clinical and myopathological phenotype. In: Brain: a journal of neurology. Volume 128, Pt 10, October 2005, pp. 2315-2326, ISSN  1460-2156 . doi: 10.1093 / brain / awh576 . PMID 15947064 .